HE ERC Proof of Concept Grant 2024-2025

Biomimetic Sensorized Barriers-on-a-Chip: Unveiling a new Generation of Market-Ready Investigation Tools

Sommario: The lack of reliable in vitro pre-clinical models represents a critical aspect unanimously recognized by the scientific community as detrimental in the pathway of bringing new medications from the laboratory to the bedside: addressing this issue would provide immense benefits to drug discovery and development processes, by ethically limiting animal testing and drastically reducing costly failures in clinical trials. To date, most in vitro models fail at recapitulating the physiological microenvironment, and this often results in misleading data withdrawal. Starting from my prototype of real scale, dynamic and biomimetic blood-brain barrier model, in this project I aim at the validation of my system, after an upgrade step consisting in embedding sensing features in the platform, thus allowing a real-time evaluation of barrier formation and integrity maintenance. Characterized by microcapillary size/fenestrations and fluid flows similar to the in vivo physiological barrier, my tool will represent a drastic innovation over other well-established models in the literature and available on the market, allowing a reliable reproduction of the physiological environment and an accurate estimation of the amount of drug and/ or nanomaterial concentration delivered through the barrier. Validation will be performed in relevant conditions, by implementing stroke and brain cancer models. All artificial components will be fabricated through two-photon polymerization (2pp), a disruptive mesoscale lithography technique that allows the fast fabrication of low-cost structures with resolution up to the nanometer scale, as well as great levels of scaffold reproducibility/accuracy. The proposed platform can be easily adopted in research laboratories and pharmaceutical industries as an advanced pre-clinical model, the primary biomedical applications of which consist in reliable screenings of drugs against pathologies of the central nervous system.

Total budget: 150.000,00€

Total contribution: 150.000,00€

HE ERC Proof of Concept Grant 2023-2024

Advanced 3D in vitro models based on magnetically-driven docking of modular microscaffolds

Sommario: This project is focused on the design, the production, the characterization, and the proposal for future commercialization of 3D modular co-culture systems, specifically designed to recapitulate the physio-pathological microenvironment of brain tumor. The key technology at the base of the proposed project is the design of magnetic microscaffolds and their fabrication through two-photon polymerization (2pp), a disruptive mesoscale manufacturing technique that enables lowcost obtainment of microstructures with nanometric resolution, characterized by unprecedented levels of accuracy and reproducibility. A microtubular structure scaffolding endothelial cells and connected to a fluidic system will be exploited to mimic the blood-brain barrier: this biohybrid device will be the base for the assembly of ferromagnetic “microcages” hosting glioblastoma cells, and will be provided with docking systems for superparamagnetic “microcages” carrying undifferentiated and differentiated neuronal progenitor cells. This approach represents a disruptive innovation with respect to other 3D models available in the literature, as it will allow a faithful recapitulation of the complex glioblastoma microenvironment through a platform that can be very easily handled in any laboratory. High-throughput screenings of brain drugs and in vitro testing of the efficacy of different anticancer therapies are envisaged upon successful accomplishment of the project, leading to a pioneering generation of flexible multi-cellular platforms easily adaptable to the mimicry of different pathological conditions.

Total budget: 150.000,00€

Total contribution: 150.000,00€

H2020 ERC - Proof of Concept Grant 2019-2020

Advanced in vitro physiological models: Towards real-scale, biomimetic and biohybrid barriers-on-a-chip

Sommario: This project is focused on the design, the production, the characterization, and the proposal for future commercialization of the first 1:1 scale 3D-printed realistic model of the brain tumor microenvironment with its associated blood neurovasculature. The proposed biomimetic dynamic 3D system, characterized by microcapillary diameter size and fluid flows similar to the in vivo physiological parameters, represents a drastic innovation with respect to other models well-established in the literature and available on the market, since it will allow to reliably reproduce the physiological environment and to accurately estimate the amount of drugs and/or of nanomaterialassociated compounds delivered through a modular length of the system. At the same time, in vitro 3D models are envisioned, allowing more physiologically-relevant information and predictive data to be obtained. All the artificial components will be fabricated through advanced lithography techniques based on two-photon polymerization (2pp), a disrupting mesoscale manufacturing approach which allows the fast fabrication of low-cost structures with nanometer resolution and great levels of reproducibility/accuracy. The proposed platform can be easily adopted in cell biology laboratories as multi-compartmental scaffold for the development of advanced co-culture systems, the primary biomedical applications of which consist in high-throughput screening of brain drugs and in testing of the efficacy of different anticancer therapies in vitro.

Total budget: 150.000,00€

Total contribution: 150.000,00€

H2020 ERC - Starting Grant 2017-2022

Magnetic Solid Lipid Nanoparticles as a Multifunctional Platform against Glioblastoma Multiforme

Sommario: Central nervous system (CNS) tumors are an important cause of morbidity and mortality worldwide. Among them, glioblastoma multiforme (GBM) is the most aggressive and lethal, characterized by extensive infiltration into the brain parenchyma. Under the standard treatment protocols, GBM patients can expect a median survival of 14.6 months, while less than 5% of patients live longer than 5 years. This poor prognosis is due to several factors, including the highly aggressive and infiltrative nature of GBM, resulting in incomplete resection, and the limited delivery of therapeutics across the blood-brain-barrier (BBB). The present project aims at addressing these therapeutic challenges by proposing a nanotechnology-based approach for the treatment of GBM, focused on the selective uptake of drug-loaded multifunctional magnetic solid lipid nanoparticles (SLNs). An external magnetic guidance will help the SLN accumulation on the cerebral endothelium, where, owing to their lipid nature, they will be allowed to enter the CNS. Here, appropriate surface ligands will drive their internalization inside cancer cells. The chemotherapeutic payload will undergo release, allowing a targeted pharmaceutical treatment that will be combined to hyperthermia upon appropriate radiofrequency application. A synergic attack against GBM will thus be performed, consisting of a chemical attack thanks to the drug, and a physical attack thanks to hyperthermia, that will dramatically enhance the possibilities of therapeutic success. By demonstrating the effectiveness of the platform to cross the BBB and to support tumor regression, a huge impact on human healthcare is envisioned. Moreover, further outcomes of this project are expected by considering the development of nanotechnology-based, multi-functional solutions that can easily be adapted to many other highimpact diseases, in particular at the brain level, where BBB crossing poses a crucial obstacle to many therapeutic approaches

Total budget: 1.412.234,64€

Total contribution: 1.412.234,64€